Atypical antipsychotic drugs are a class of drugs used to treat psychiatric conditions such as schizophrenia, acute mania and bipolar disorders. Some of the early or typical antipsychotic drugs exhibited a number of undesirable side effects such as acute dyskinesias, acute dystonias, motor restlessness, pseudo-Parkinsonism and tardivedyskinesias. These adverse side effects have been referred to as extrapyramidal symptoms.
In an effort to overcome these extrapyramidal symptoms, a group of compounds were developed that are commonly referred to as atypical antipsychotic drugs. These atypical antipsychotic drugs are generally heterocyclic compounds that affect the serotonin and dopamine receptors. Examples of some atypical antipsychotic drugs include clozapine, olanzapine, risperidone, quetiapine, ziprasidone, paliperidone, aripiprazole, asenapine, iloperidone, sertindole, zotepine, amisulpride bifeprunox, melperone and pharmaceutically acceptable salts thereof.
Pharmaceutical dosage forms containing atypical antipsychotic drugs have been described in the literature. For example, the 61st edition of the Physicians' Desk Reference, © 2007 (“PDR”), describes commercially available RISPERDAL® products which are oral solutions, tablets, orally disintegrating tablets and microsphere-containing injections that contain risperidone (see PDR at pages 1676-1688); ABILIFY® products which are oral solutions, tablets and orally disintegrating tablets that contain aripiprazole (see PDR at pages 2450-2455) and GEODON® capsules and injections. Some of these formulations employ organic acids such as citric, tartaric and benzoic acids.
U.S. Pat. No. 5,563,134 discloses clozapine dosage forms that contain an acid scavenger such as ascorbic acid. The ascorbic acid is reported to reduce the occurrences of granulocytopenia or agranulocytosis that is known to occur with the administration of clozapine. U.S. Pat. No. 6,251,895 discloses olanzapine dosage forms that contain benzoic acid. Olanzapine is also commercially available under the tradename ZYPREXA® in an intramuscular formulation that employs tartaric acid.
U.S. Pat. No. 5,948,437 discloses a number of quetiapine dosage forms and indicates organic acids or alkali metals salts of the organic acids may be used as pH modifiers in the dosage forms. Although a number of organic acids are disclosed in this patent, it is reported that the alkali metal salts such as sodium citrate are preferred.
Although many pharmaceutical dosage forms containing atypical antipsychotic drugs have been described in the art, it is an object of the present invention to provide a pharmaceutical composition comprising an atypical antipsychotic drug and an organic acid selected from the group consisting of succinic acid, fumaric acid or mixtures thereof. It is believed that the use of these non-metal, dual carboxyl group organic acids improve the stability of the atypical antipsychotic drug.
It is another object of the present invention to provide a pharmaceutical dosage form comprising an atypical antipsychotic drug and an organic acid selected from the group consisting of succinic acid, fumaric acid or mixtures thereof that can be administered orally.
It is yet another object of the present invention to provide a controlled release pharmaceutical dosage form comprising an atypical antipsychotic drug and an organic acid selected from the group consisting of succinic acid, fumaric acid or mixtures thereof.
It is still a further object of the present invention to provide a controlled release pharmaceutical dosage form comprising an atypical antipsychotic drug and an organic acid selected from the group consisting of succinic acid, fumaric acid or mixtures thereof that is free of any swelling or hydrogel polymeric materials.
These and other objects of the present invention will become apparent from a review of the appended specification.